Screening patients for subclinical atherosclerosis with non-contrast cardiac CT

Accurate risk assessment may be helpful in decreasing cardiovascular events through more appropriate targeting of preventive measures. Traditional risk assessment may be refined with the selective use of coronary artery calcium score (CACS) or other methods of subclinical atherosclerosis measurement. This article reviews information pertaining to the clinical use of CACS for assessing coronary atherosclerosis as a useful predictor of coronary artery disease (CAD) in certain population of patients. Coronary calcification is a marker of atherosclerosis that can be quantified with the use of cardiac CT and it is proportional to the extent and severity of atherosclerotic disease. The published studies demonstrate a high sensitivity of CACS for the presence of coronary artery disease but a much lower specificity for obstructive CAD depending on the magnitude of the CACS. Several large clinical trials have found clear, incremental predictive value of CACS over the Framingham risk score when used in asymptomatic patients. However, early detection of CAD by Electron Beam Tomography (EBT) screening has not convincingly demonstrated a reduction in mortality and morbidity. Nevertheless, relevant prognostic information obtained may be useful to initiate or intensify appropriate treatment strategies to slow the progression of existing atherosclerotic vascular disease. Current data suggest intermediate-risk patients may benefit most from further risk stratification with cardiac CT, as CAC testing is effective at identifying increased risk and in one study motivating effective behavioral changes. Randomized clinical trials will help determine if selective use of cardiac CT in the intermediate-risk patient would lead to more appropriate use of pharmacologic therapy and improved clinical outcomes.     

冠状动脉钙化研究进展

冠状动脉钙化是动脉粥样硬化的一个重要的危险因素,多项研究揭示冠状动脉钙化和粥样硬化斑块负荷有着密切的关系,因此冠状动脉钙化程度的测量在预测未来心血管事件及死亡率中起着重要的作用。现将通过对冠状动脉钙化的危险因素、发病机制、冠状动脉钙化积分评测及方法、钙化与心血管疾病的关系、冠状动脉钙化与肾脏疾病的关系、冠状动脉钙化与全因死亡及钙化的治疗等方面做一综述。     

Coronary risk assessment using traditional risk factors with CT coronary artery calcium scoring in clinical practice

As coronary artery calcium (CAC) is atherosclerosis and not just a marker of cardiovascular (CV) disease, measurement of a patient's coronary artery calcium score (CACS) is a strong predictor of risk. Clinically performed in asymptomatic patients, the CACS, along with several CV risk factors, namely age, sex, ethnicity, diabetes, tobacco use, family history, cholesterol level, blood pressure, and use of cholesterol or hypertensive medications, provide a predictive model of 10 year risk for CV events. A smartphone “App” makes this quick to obtain and use. This helps the clinician in making recommendations for both lifestyle changes and statin therapy. Those patients in which the most benefit occur from measurement of a CACS are those at an intermediate CV risk. Measurement of the CACS has become an integral part of the clinician's assessment of a patient's CV risk and for guiding preventative therapies.     

Coronary Artery Calcium: Where Do We Stand After Over 3 Decades?

In 2018, cardiovascular society cholesterol guidelines recommended the use of coronary artery calcium to guide statin therapy in patients 40-79 years of age who are at intermediate risk by multiple risk factor equations (ie, estimated 10-year risk for atherosclerotic disease of 7.5%-19.9% but in whom statin benefit is uncertain). Many such patients have no coronary calcium and remain at <5% risk over the next decade; hence, statin therapy can be delayed until a repeat calcium scan is conducted. Exceptions include patients with severe hypercholesterolemia, diabetes, and a strong family history of atherosclerotic disease. If coronary calcium equals 1-99 Agatston units, the 10-year risk is borderline (5% to <7.5%) and statin therapy is optional pending a repeat scan. If coronary calcium equals 100-299 Agatston units, the patient is clearly statin eligible (7.5% to <20% 10-year risk). And finally, if coronary calcium is ≥300 Agatston units, a patient is at high risk and is a candidate for high-intensity statins. Risk factor analysis combined judiciously with coronary calcium scanning offers the strongest evidence-based approach to use of statins in primary prevention.     

The association of coronary calcium score and conventional cardiovascular risk factors in Type 2 diabetic subjects asymptomatic for coronary heart disease (The PREDICT Study).

AIM: To determine the association between coronary calcification score (CACS) obtained by electron beam computed tomography (EBCT) and cardiovascular risk factors in Type 2 diabetic subjects entered into a prospective cohort study. METHODS: Type 2 diabetic subjects attending routine hospital diabetic clinics without known coronary heart disease (CHD) underwent EBCT to measure CACS. Demographic data were obtained and conventional cardiovascular risk factors were measured at baseline. RESULTS: Four hundred and ninety-five subjects were assessed of whom 67.7% were male. They had a mean (SD) age of 62.9 (7.1) years, with median (inter-quartile range) duration of diabetes of 8 (4-13) years. None had a history of coronary artery disease. Forty-five per cent were receiving lipid-lowering agents (including 36% statins). In a univariate analysis, there were significant associations between increased CACS and age, duration of diabetes, male gender, waist-hip ratio (WHR), systolic blood pressure, and the use of statins. In a multivariate model adjusting for the possible interaction of these and other factors, the significant association between CACS and WHR, systolic blood pressure, male gender and statin use remained. CONCLUSIONS: The close association between CACS and WHR and the association with systolic blood pressure suggest that coronary calcification may be particularly linked to the metabolic syndrome in Type 2 diabetes.     

冠状动脉CT造影评估冠状动脉钙化进展及临床意义

冠状动脉粥样硬化是冠心病的病理学基础,而冠状动脉钙化是粥样硬化病变的重要标志。检测和评估冠状动脉钙化不仅对预测心血管事件有重要意义,还有助于了解疾病进展,从而更好地指导临床诊治。冠状动脉CT造影(CCTA)是对冠状动脉钙化斑块进行精确量化评估的无创检查手段,其对于定量冠状动脉钙化以及预后评估具有重要的临床价值。本文对冠状动脉钙化CCTA检测方法及其临床应用等进行综述。     

Italian Chapter of the International Society of Cardiovascular Ultrasound expert consensus document on coronary computed tomography angiography: overview and new insights

Coronary computed tomography angiography is a noninvasive heart imaging test currently undergoing rapid development and advancement. The high resolution of the three‐dimensional pictures of the moving heart and great vessels is performed during a coronary computed tomography to identify coronary artery disease and classify patient risk for atherosclerotic cardiovascular disease. The technique provides useful information about the coronary tree and atherosclerotic plaques beyond simple luminal narrowing and plaque type defined by calcium content. This application will improve image‐guided prevention, medical therapy, and coronary interventions. The ability to interpret coronary computed tomography images is of utmost importance as we develop personalized medical care to enable therapeutic interventions stratified on the bases of plaque characteristics. This overview provides available data and expert's recommendations in the utilization of coronary computed tomography findings. We focus on the use of coronary computed tomography to detect coronary artery disease and stratify patients at risk, illustrating the implications of this test on patient management. We describe its diagnostic power in identifying patients at higher risk to develop acute coronary syndrome and its prognostic significance. Finally, we highlight the features of the vulnerable plaques imaged by coronary computed tomography angiography.     

Advanced Lipid Thinking Prior to Incorporating Advanced Lipid Testing

Lipid profiles help estimate patient’s short- and long-term atherosclerotic cardiovascular disease risk over the life course and inform treatment decisions. Advanced lipid testing can provide additional information in selected patients. New 2018 cholesterol guidelines suggest which patients may benefit from additional testing. In patients ages 40-75 years, calculation of a 10-year atherosclerotic cardiovascular disease risk score begins the clinician–patient risk discussion. In those at intermediate risk (10-year risk 7.5%-19.9%) for future events, inclusion of enhancing factors personalizes the risk decision. The guidelines identify enhancing factors that can support initiating statin therapy. Two advanced lipid tests may be used. Apolipoprotein B levels improve risk estimations and identify genetic disorders in hypertriglyceridemic patients. In patients with a family history of premature atherosclerotic cardiovascular disease, significantly elevated lipoprotein (a) levels may reclassify risk. The decision-making cascade of estimating 10-year risk, personalizing risk status with risk-enhancing factors, and, if appropriate, reclassifying risk with a coronary artery calcium score is advanced lipid thinking that can utilize advanced lipid testing to optimize atherosclerotic cardiovascular disease prevention.     

冠状动脉钙化积分预测老年冠心病的相关研究

目的进一步探讨预测老年冠心病的新指标,预防心血管事件的发生。方法对≥60岁老年人66例(冠心病48例,非冠心病18例)进行多层螺旋CT(MSCT)冠状动脉扫描和计算机自动测定冠状动脉钙化积分(CACS),对CACS结果进行分析。结果老年冠心病组的CACS明显高于非冠心病组(P<0·01)。3支血管钙化者CACS明显高于1支及2支血管钙化者,且钙化发生在任意血管段都有明确意义(P<0·01,P<0·05)。结论CACS优于传统危险因子,可作为预测冠心病的新指标之一。     

Association between low serum free thyroxine concentrations and coronary artery calcification in healthy euthyroid subjects

Background: Considerable evidence suggests that hypothyroidism could promote atherosclerotic vascular changes. We planned this study to investigate whether serum free thyroxine (FT4) or thyroid-stimulating hormone (TSH) levels are associated with coronary artery calcification measured in healthy euthyroid subjects. Methods: A cross-sectional analysis was performed among subjects who visited our hospital for a health checkup. Among 1849 subjects, 669 (mean age 55.3±8.8 years; 392 men) with FT4 and TSH in the normal ranges were included after excluding those with diabetes, a history of current smoking and cardiovascular disease (CVD), or the use of drugs for hypertension, antithyroid drugs, or thyroid hormone preparations. Coronary artery calcium scores (CACS) were measured by multi-detector computed tomography. Results: Subjects with a CACS >100 had lower FT4 levels than those with a lower CACS (p=0.017), whereas no difference was observed in the TSH levels among CACS categories. FT4 levels had an odds ratio of 0.06 for high CACS (95% confidence interval=0.01-0.74; p=0.028) after the adjustment for CVD risk factors. In multivariate regression analysis, CACS was negatively correlated with FT4 levels (β=-0.823, p=0.032), and the inverse association between FT4 and CACS remained significant only in men (p=0.011). Conclusion: FT4 levels were inversely associated with coronary artery calcification in euthyroid healthy subjects, especially in men independent of conventional CVD risk factors. Further studies are needed to validate whether subjects with decreased FT4 levels within the normal reference range are at a high CVD risk and have poor cardiovascular outcomes.     

Coronary artery calcium and cardiovascular risk in diabetes

Measurement of coronary artery calcium score (CACS) by electron beam tomography has been shown to a powerful predictor of coronary heart disease events in asymptomatic non-diabetic subjects. In type 2 diabetes, measurement of CACS was found to be a powerful predictor of cardiovascular events which could enhance prediction provided by established risk models. 23% of type 2 diabetic subjects with low CACS were found to be at low risk for cardiovascular events. Moreover mortality was similar for type 2 diabetic and non-diabetic subjects with undetectable coronary artery calcification. Conversely type 2 diabetic subjects with high CACS were identified who were at high cardiovascular risk. Thus not all those with type 2 diabetes are at similar cardiovascular risk. Measurement of CACS enables cardiovascular risk in type 2 diabetes to be stratified so that the level of preventive therapy could be reduced in some and intensified in others. Although prospective data for the power of CACS to predict CHD events in type 1 diabetes are lacking, measurement of CACS could help in deciding on preventive therapy in type 1 diabetes.     

Role of Coronary Artery Calcium Score and Coronary CT Angiography in the Diagnosis and Risk Stratification of Individuals with Suspected Coronary Artery Disease

Coronary heart disease is the leading cause of death worldwide, and has traditionally been assessed through a patient’s cardiovascular risk profile that is comprised of a combination of genetic, social, physiologic, and environmental factors. A growing discordance is being recognized in the ability of current risk estimation tools to predict outcomes versus that of actual measured outcomes. Exciting new improvements in technology have made noninvasive imaging modalities of the heart—in particular, coronary artery calcium score (CACS) and coronary computed tomography (CT) angiography—an increasingly important component in the diagnosis of ischemic heart disease. The CACS has been found to be a marker of vascular injury that correlates closely with overall atherosclerotic burden, whereas coronary CT angiography permits detection of noncalcified plaque coronary artery stenosis severity. A growing body of literature has developed detailing the valuable prognostic utility of these tests in the management of patients and how they may 1 day be used to complement current risk prediction models.     

The association between extracoronary calcification and coronary artery disease in patients with type 2 diabetes mellitus

Cardiovascular complications are the major cause of diabetes-associated morbidity and mortality. However, not all patients with diabetes are at increased risk for cardiovascular disease (CVD). Coronary artery calcification was found to be a powerful predictor of coronary artery disease (CAD). The presence of extracoronary cardiac calcification as a useful predictor of CAD is not yet established, especially in type 2 diabetes mellitus (T2DM). The aim of this study was to evaluate the relation between extracoronary calcification and extent of CAD in a group of T2DM patients who were scheduled for computed tomographic coronary angiography (CTCA). We prospectively studied 380 patients (151 had T2DM) under the age of 60 years who were scheduled for CTCA because of suspected CAD. Severity of CAD was assessed by Gensini score. Coronary artery calcium score (CACS) as well as calcium score in the aortic valve, mitral annulus, ascending aorta, and descending aorta were measured by a 256-row multidetector computed tomography scanner with dedicated software for calcium calculation. Patients with known CAD were excluded. Diabetic and nondiabetic patients had comparable age and gender distribution. However, the diabetic group had higher Gensini score, CACS, and extracoronary calcium score (ECCS). Logistic regression analyses identified male gender and ECCS as significant predictors for the presence of CAD in diabetic patients. Age, smoking, and ECCS were the significant predictors of CAD in nondiabetic patients. Type 2 diabetic patients had increased coronary and extracoronary calcification. ECCS was found to be a significant predictor of CAD in diabetic and nondiabetic patients only when CACS was not taken into account.     

Evaluation of coronary calcium score by multidetector computed tomography in relation to endothelial function and inflammatory markers in asymptomatic individuals.

BACKGROUND: Coronary calcification has been correlated with the presence and extent of coronary artery disease (CAD), so in the present study the associations between coronary artery calcification score (CACS) and endothelial dysfunction, as well as the important inflammatory markers C-reactive protein (CRP), interleukin (IL)-6, and oxidized low-density lipoprotein (OxLDL), were studied in asymptomatic individuals at intermediate risk for CAD. METHODS AND RESULTS: The study group comprised 177 subjects (103 males) aged 50.6+/-5.9 years. CACS was measured by multidetector computed tomography using the Agatston method. Endothelium-dependent flow-mediated dilatation (FMD) and endothelium-independent nitroglycerin-mediated dilatation (NMD) were measured by high-resolution external brachial ultrasound. Coronary artery calcification (CAC) was detected in 82 subjects (52 males), and the median CACS was 143 [31-311.25] units. After adjusting for gender and body mass index, log (CACS +1) correlated positively with age (r=0.401, p<0.001) and IL-6 levels (r=0.442, p<0.001), and negatively with FMD (r=-0.511, p<0.001). The correlations of log (CACS +1) with CRP and OxLDL levels, and with NMD, were non-significant. In a multivariate-adjusted logistic regression model, age (odds ratio (OR) =1.083 [1.014-1.156]), serum IL-6 level (OR=3.837 [2.166-6.798]) and FMD (OR=0.851 [0.793-0.913]) were significantly and independently associated with CAC. CONCLUSIONS: Peripheral endothelial function inversely correlated with CACS, whereas IL-6 level was associated with CACS. Testing for endothelial function and IL-6 level may improve cardiovascular risk assessment and help target the therapeutic strategies in asymptomatic patients at intermediate CAD risk.     

Relationship of subclinical coronary atherosclerosis and National Cholesterol Education Panel guidelines in asymptomatic Brazilian men

BACKGROUND AND OBJECTIVE: Coronary heart disease (CHD) is the leading cause of death worldwide including Brazil. Improved precision in detecting early coronary disease may aid in more targeted preventive therapy. The National Cholesterol Education Program (NCEP) provides guidelines for determining the aggressiveness of primary prevention strategies including lipid lowering based on Framingham risk equation. Identification of subclinical atherosclerosis and coronary plaque burden is a step towards identifying high-risk individuals. This investigation was designed to determine how the updated NCEP guidelines classify asymptomatic individuals with presence of any as well as advanced CACS (coronary artery calcium score), a powerful intermediary for CHD events, in asymptomatic Brazilian men. METHODS AND RESULTS: Five hundred forty-six asymptomatic Brazilian men (mean age: 46+/-7 years) presented to a single electron beam tomography (EBT) facility in Sao Paulo. The study population was categorized into low risk (0-1 risk factors, n=166, 30%), intermediate risk (> or = 2 risk factors but < 10% risk of CHD over 10 years, n=150, 27%), moderately high risk (2 risk factors and 10-20% risk of hard CHD events in 10 years, n=147, 28%) and high-risk (> or = 2 risk factors and > 20% risk of hard CHD events in 10 years, n=83, 15%), respectively. In our study population, overall no CACS, mild CACS (1-99.9), moderate-severe CACS (> or = 100) were observed in 317 (58%), 160 (29%) and 69 (13%) men, respectively. Advanced calcification (CACS > or = 75th percentile for age) was present in 19% (n=104) men. Based on the LDL-C cutoffs recommended by the NCEP guidelines for initiation of lipid lowering, overall only 55% with CACS > or = 100 and 42% men with CACS > or = 75th percentile qualified for pharmacotherapy. As a result nearly half of individuals with CACS > or = 100 (45%) and CACS > or = 75th percentile (48%) missed eligibility for drug therapy. CONCLUSION: Our findings reveal the potential limitation of NCEP guidelines in identifying asymptomatic Brazilian men with significant coronary atherosclerosis who are potential candidates for aggressive primary prevention. Assessment of CACS may provide incremental value to global risk assessment in high-risk Brazilian men.     

Coronary calcification, homocysteine, C-reactive protein and the metabolic syndrome in Type 2 diabetes: the Prospective Evaluation of Diabetic Ischaemic Heart Disease by Coronary Tomography (PREDICT) Study.

AIMS: The PREDICT Study aims to determine: (i) the association between cardiovascular risk factors and coronary artery calcification score (CACS) obtained by electron beam tomography and (ii) the predictive value of CACS for coronary heart disease (CHD) events in Type 2 diabetes. METHODS: Having previously reported relationships between CACS and conventional risk factors, we have now studied the novel risk factors, plasma high-sensitivity C-reactive protein (CRP) and homocysteine, insulin resistance, serum apoprotein A1 and B concentrations, the serum triglyceride/high-density lipoprotein cholesterol ratio and metabolic syndrome (International Diabetes Federation definition) in 573 subjects of the PREDICT Type 2 diabetes cohort. RESULTS: In univariate analyses, the only significant positive novel correlate of CACS was homocysteine (P = 0.0004). CRP was increased in those with detectable calcification, but decreased with increasing calcification score (P = 0.006). In a multivariate model that included all significant univariate correlates, CACS was independently associated with age (P < 0.0001), waist-hip ratio (P < 0.02), male gender (P < 0.05) and duration of diabetes (P < 0.05), but the association with homocysteine was no longer significant. The negative association between CACS and CRP remained in multivariate analysis, and was independent of statin use. CONCLUSIONS: Age was the major factor influencing CACS in Type 2 diabetes, with weaker contributions from waist hip-ratio and duration of diabetes. Other novel cardiovascular risk factors appear to have little positive effect.     

Coronary risk assessment using traditional risk factors with computed tomography coronary artery calcium scoring: Illustrative cases

A patient's coronary artery calcium score (CACS) is a strong independent predictor of cardiovascular risk. Used in conjunction with traditional measures of risk, the CACS helps the clinician discuss cardiovascular (CV) risk and recommend therapies with the patient. We present several cases in which measurement of the CACS and traditional risk factors were used to help guide the clinician–patient conversation and guide therapies.     

Risk Stratification and Selection for Statin Therapy: Going Beyond Framingham

Decisions for statin therapy in the primary prevention of atherosclerotic cardiovascular disease are generally made using the 10-year Framingham Risk Score (FRS). Even when a family history of premature cardiovascular disease is taken into account, there is often ambiguity about the need for statin therapy for patients with a 10-year FRS of 5%-19% and low-density lipoprotein cholesterol <3.5 mmol/L. Current Canadian dyslipidemia guidelines recommend consideration of a diversity of other factors, including biochemical measurements and imaging studies to help determine whether the calculated FRS might be misleadingly low and whether statin therapy might, therefore, be prudent. However, efficient use of the plethora of secondary factors makes this decision process itself potentially ambiguous. This brief summary provides a practical approach for using clinical information, basic biochemical tests, and more specialized tests, such as carotid ultrasound and coronary artery calcium scoring, to identify groups of patients at greater risk for atherosclerotic cardiovascular disease than suggested by the FRS.     

Clinical characteristics of coronary artery calcification in diabetic patients

Coronary artery calcification is frequently seen in cardiovascular disease in diabetic patients, and usually indicates the severity of coronary stenosis. They occur in the intima of the lipid-rich atherosclerotic coronary lesions. The mechanism of the coronary calcification is still not known, though several proteins such as AGE are thought to induce the calcium accumulation in the atheroma.     

Doença coronária não obstrutiva documentada por tomografia computorizada cardíaca: contraste entre a carga aterosclerótica e o risco cardiovascular

Cardiac computed tomography (CT) documents the presence of coronary artery disease, regardless of the degree of stenosis. The prognostic value of non-obstructive coronary artery disease documented by cardiac CT has recently been validated. However, there are still no clear guidelines on the management of such patients, particularly concerning initiation of more aggressive pharmacological measures for primary prevention. The approach to these patients remains controversial, especially in cases in which there is a discrepancy between cardiovascular risk and the atherosclerotic burden as documented by cardiac CT.The authors describe the case of a patient with a discrepancy between the extent of documented coronary atherosclerosis and that estimated according to pretest probability and cardiovascular risk scores. As this individual had more severe coronary atherosclerosis than expected (calcium score above the 90th percentile and non-obstructive coronary artery disease on cardiac CT) but was a competitive athlete and otherwise asymptomatic and without risk factors or cardiovascular history, with a very low estimated cardiovascular risk, it was difficult to decide on the risks and benefits of pharmacological primary prevention.